Antidepressants

Annette (Gbemudu) Ogbru, PharmD, MBA

Dr. Gbemudu received her B.S. in Biochemistry from Nova Southeastern University, her PharmD degree from University of Maryland, and MBA degree from University of Baltimore. She completed a one year post-doctoral fellowship with Rutgers University and Bristol Myers Squibb.

Jay W. Marks, MD

Jay W. Marks, MD, is a board-certified internist and gastroenterologist. He graduated from Yale University School of Medicine and trained in internal medicine and gastroenterology at UCLA/Cedars-Sinai Medical Center in Los Angeles.

What are antidepressants and how do they work?

Antidepressants are a class of drugs that reduce symptoms of depressive
disorders by correcting chemical imbalances of neurotransmitters in the brain.
Chemical imbalances may be responsible for changes in mood and behavior.

Neurotransmitters are vital, as they are the communication link between nerve
cells in the brain. Neurotransmitters reside within vesicles found in nerve
cells, which are released by one nerve and taken up by other nerves.
Neurotransmitters not taken up by other nerves are taken up by the same nerves
that released them. This process is called "reuptake." The prevalent
neurotransmitters in the brain specific to depression are serotonin,
dopamine and norepinephrine (also called noradrenaline).

In general, antidepressants work by inhibiting the reuptake of specific
neurotransmitters, hence increasing their levels around the nerves within the
brain, such as selective serotonin reuptake inhibitors (SSRIs), antidepressants
that will affect serotonin levels in the brain.

Are there differences among antidepressants?

Antidepressants differ in their effects on neurotransmitters, established uses, adverse effects and drug
interactions. All antidepressants that are used for depression are effective;
there is no evidence that one antidepressant is more effective than another. However, patients may respond to or tolerate one antidepressant, and not respond
to or tolerate another antidepressant.

What are side effects of antidepressants?

Antidepressants that belong to the same class of antidepressant produce similar side effects. Antidepressants may cause withdrawal symptoms if abruptly
discontinued. Withdrawal symptoms include nausea, vomiting, dizziness,
headache, irritability, sleep disturbance, nightmares, psychosis, and
seizures. All antidepressants have a warning about use in children and adolescents.
Antidepressants increased the risk of suicidal thinking, and suicidal behavior in short-term studies in children and adolescents with depression and other
psychiatric disorders. Anyone considering the use of antidepressant in a child or adolescent must balance this risk of
suicide with the clinical need for the drug. Patients who are started on therapy should be closely observed for
clinical worsening, suicidal thoughts or unusual changes in behavior.

What are the possible drug interactions? Tricyclic antidepressants (TCAs)

Combining tricyclic antidepressants (TCAs) with clonidine (Catapres) may lead to dangerous elevations in blood pressure because TCA may inhibit the antihypertensive effect of clonidine.
Combining TCAs with carbamazepine (Tegretol) may result in lower TCA blood levels and higher carbamazepine levels, leading to decreased TCA efficacy or increased carbamazepine toxicity. TCAs may increase the effects of epinephrine,
norepinephrine and dopamine. Dangerous increases in blood pressure and abnormal heartbeats may occur. Cimetidine (Tagamet) may reduce the breakdown of some TCAs [for example, amitriptyline (Elavil)] and potentially lead to increased side effects.

Selective serotonin reuptake inhibitors (SSRIs) interactions

Selective serotonin reuptake inhibitors (SSRIs) should not be combined with other drugs that increase brain serotonin
levels [for example, MAOIs, TCAs, sumatriptan (Imitrex),
linezolid (Zyvox), St John's Wort, amphetamines]
because there is a risk of dangerous adverse effects. The risk of gastrointestinal bleeding may be increased when SSRIs are combined with nonsteroidal antiinflammatory drugs (NSAIDs).

Monoamine oxidase inhibitors (MAOIs) interactions

Monoamine oxidase inhibitors (MAOIs) should not be combined with other antidepressants or other drugs that increase serotonin levels [for example, amphetamines, linezolid (Zyvox), St. Johns Wort,
sumatriptan (Imitrex)]. Such combinations cause excessive serotonin levels in the brain, which may lead to confusion, high blood pressure, tremor, hyperactivity, coma, and death. Administration of MAOIs and other antidepressants or drugs that
elevate serotonin should be separated by 14 days. Administration of MAOIs with epinephrine, norepinephrine, phenylephrine, pseudoephedrine, and dopamine may lead to hypertensive crisis. MAOIs interact with tyramine containing foods,
resulting in a hypertensive crisis.